Use of models in understanding the mechanism of action of haemoglobin

Models with three, four and eight salt-bridges have been used to study the mechanism of action of haemoglobin. Both side chains forming a salt-bridge, i.e. the proton acceptor and the proton donor, are postulated to change pK on ligation of oxygen. The eight salt-bridge model is able to predict, as a unified theory, both the degree of oxygenation and the Bohr effect at any PH and p_O2 value; this has not been done by any other published model. The predicted pK values for the Borh groups corresponde well with those measured experiemntally. This model predicts the pK values of those side chains responsible for the acid Bohr effect, suggesting that these correspond to the proton acceptors of the salt-bridges. The model also fulfils the condition of linearity between the fractional degree of oxygenation and fractional number of protons released. It is postulated that there is a gradual change in structure on going from deoxy to oxyhaemoglobin, due to the rupture of salt-bridges. The path folowed during this process will be both pH and p_O2 dependent. A formula describing the number of intact or broken salt-bridges as a function of pH and p_O2 was developed. This formula shows that the fractional number of broken salt-bridges reaches a minimum value of 0.2 at around pH 6.3 in the absence of oxygen. However, if oxygen is added, this fractional number approaches 1.0 soon after the partial pressure of oxygen goes above 40 mm Hg.